In the Journals

Prolonged ADT may improve survival in high-Gleason grade prostate cancer

Amar U. Kishan

Prolonged androgen deprivation therapy was associated with improved survival among men with Gleason grade groups 4 and 5 prostate cancer, but optimal treatment durations varied, according to findings from a meta-analysis of patient outcomes.

Amar U. Kishan, MD, assistant professor of radiation oncology and urology at University of California, Los Angeles, and colleagues analyzed data on 593 men with Gleason grade group 4 (GG4) and 399 men with Gleason grade group 5 (GG5) prostate cancer who had been enrolled in six randomized controlled trials. Clinicians followed the men for a median of 6.4 years to determine survival outcomes associated with radiotherapy alone, short-term ADT (4 to 6 months), long-term ADT (28 to 36 months) and lifelong ADT.

“Lifelong ADT is poorly tolerated and not palatable for many patients, particularly those who are presenting with localized disease,” Kishan told HemOnc Today. “Further, we know from other data — for example, retrospective data examining the use of extreme dose escalation — that lifelong ADT is not necessary to obtain cancer control in patients with GG5 disease. However, because there is clearly a biological synergy between ADT and radiotherapy in lower-grade disease, and GG5 disease is not inherently resistant to hormonal therapy, a major implication is that more potent ADT agents, such as apalutamide (Erleada, Janssen Oncology), enzalutamide (Xtandi; Astellas, Pfizer Oncology) or abiraterone (Zytiga, Janssen Oncology), might allow the recapitulation of the benefit seen from lifelong ADT but with a shorter duration of use.”

Among the GG4 group, compared with radiotherapy alone, OS was better with short-term ADT (HR = 0.59; 95% CI, 0.38-0.93) and long-term ADT (HR = 0.43; 95% CI, 0.26-0.7) but not with lifelong ADT (HR = 0.84; 95% CI, 0.54-1.3).

Among the GG5 group, compared with radiotherapy alone, OS was better with lifelong ADT (HR = 0.48; 95% CI, 0.31-0.76) but not with short-term ADT (HR = 1.13; 95% CI, 0.69-1.87) nor long-term ADT (HR = 0.8; 95% CI, 0.45-1.44).

Men with GG5 prostate cancer had inferior OS compared with men with GG4 prostate cancer after short-term ADT (HR = 1.4; 95% CI, 1.05-1.88) and overall (HR = 1.25; 95% CI, 1.07-1.47).

Researchers observed similar OS among the GG4 and GG5 groups following long-term ADT (HR = 1.21; 95% CI, 0.89-1.65) and lifelong ADT (HR = 0.85; 95% CI, 0.53-1.37).

The researchers noted that the improvements in survival with longer ADT were seen with “different optimal durations.”

“In this study, we found that — at least in the setting of these large, practice-changing randomized trials — survival endpoints were only improved for patients with GG5 disease who received lifelong ADT, rather than short-term or long-term ADT,” Kishan said. “On the other hand, patients with GG4 disease had benefit from both short-term and long-term ADT. What this implies is that GG5 disease is not inherently insensitive to hormonal therapy — or else lifelong ADT would not offer any benefit — but rather that the synergy of ADT duration and radiotherapy has not been optimized for patients with GG5 disease.”

Kishan said the results could impact clinical strategies.

“The major implication is that there is room for improving outcomes by moving some of the advanced ADT agents from the recurrent/metastatic setting to the upfront setting,” Kishan said. “Specifically, this might be important in patients with GG5 tumors. Medical oncologists will be pivotal in moving these treatments into this setting.” – by Rob Volansky

For more information:

Amar U. Kishan, MD, can be reached at 200 UCLA Medical Plaza, Suite B265, Los Angeles, CA 90095; email: aukishan@mednet.ucla.edu.

Disclosures: Kishan reports honoraria from Varian Medical Systems Inc. Please see the study for all other authors’ relevant financial disclosures.

 

Amar U. Kishan

Prolonged androgen deprivation therapy was associated with improved survival among men with Gleason grade groups 4 and 5 prostate cancer, but optimal treatment durations varied, according to findings from a meta-analysis of patient outcomes.

Amar U. Kishan, MD, assistant professor of radiation oncology and urology at University of California, Los Angeles, and colleagues analyzed data on 593 men with Gleason grade group 4 (GG4) and 399 men with Gleason grade group 5 (GG5) prostate cancer who had been enrolled in six randomized controlled trials. Clinicians followed the men for a median of 6.4 years to determine survival outcomes associated with radiotherapy alone, short-term ADT (4 to 6 months), long-term ADT (28 to 36 months) and lifelong ADT.

“Lifelong ADT is poorly tolerated and not palatable for many patients, particularly those who are presenting with localized disease,” Kishan told HemOnc Today. “Further, we know from other data — for example, retrospective data examining the use of extreme dose escalation — that lifelong ADT is not necessary to obtain cancer control in patients with GG5 disease. However, because there is clearly a biological synergy between ADT and radiotherapy in lower-grade disease, and GG5 disease is not inherently resistant to hormonal therapy, a major implication is that more potent ADT agents, such as apalutamide (Erleada, Janssen Oncology), enzalutamide (Xtandi; Astellas, Pfizer Oncology) or abiraterone (Zytiga, Janssen Oncology), might allow the recapitulation of the benefit seen from lifelong ADT but with a shorter duration of use.”

Among the GG4 group, compared with radiotherapy alone, OS was better with short-term ADT (HR = 0.59; 95% CI, 0.38-0.93) and long-term ADT (HR = 0.43; 95% CI, 0.26-0.7) but not with lifelong ADT (HR = 0.84; 95% CI, 0.54-1.3).

Among the GG5 group, compared with radiotherapy alone, OS was better with lifelong ADT (HR = 0.48; 95% CI, 0.31-0.76) but not with short-term ADT (HR = 1.13; 95% CI, 0.69-1.87) nor long-term ADT (HR = 0.8; 95% CI, 0.45-1.44).

Men with GG5 prostate cancer had inferior OS compared with men with GG4 prostate cancer after short-term ADT (HR = 1.4; 95% CI, 1.05-1.88) and overall (HR = 1.25; 95% CI, 1.07-1.47).

Researchers observed similar OS among the GG4 and GG5 groups following long-term ADT (HR = 1.21; 95% CI, 0.89-1.65) and lifelong ADT (HR = 0.85; 95% CI, 0.53-1.37).

The researchers noted that the improvements in survival with longer ADT were seen with “different optimal durations.”

“In this study, we found that — at least in the setting of these large, practice-changing randomized trials — survival endpoints were only improved for patients with GG5 disease who received lifelong ADT, rather than short-term or long-term ADT,” Kishan said. “On the other hand, patients with GG4 disease had benefit from both short-term and long-term ADT. What this implies is that GG5 disease is not inherently insensitive to hormonal therapy — or else lifelong ADT would not offer any benefit — but rather that the synergy of ADT duration and radiotherapy has not been optimized for patients with GG5 disease.”

Kishan said the results could impact clinical strategies.

“The major implication is that there is room for improving outcomes by moving some of the advanced ADT agents from the recurrent/metastatic setting to the upfront setting,” Kishan said. “Specifically, this might be important in patients with GG5 tumors. Medical oncologists will be pivotal in moving these treatments into this setting.” – by Rob Volansky

For more information:

Amar U. Kishan, MD, can be reached at 200 UCLA Medical Plaza, Suite B265, Los Angeles, CA 90095; email: aukishan@mednet.ucla.edu.

Disclosures: Kishan reports honoraria from Varian Medical Systems Inc. Please see the study for all other authors’ relevant financial disclosures.